Defining the critical cellular elements of the stroma that support B lymphoma progression at lymphoid and non- lymphoid sites is of great therapeutic potential, yet remains an understudied area of research. The presence of follicular dendritic cells (FDCs) is a hallmark of lymphoid neogenesis in tumors, including B lymphomas. However, the functional importance of the these cells has not been addressed. Herein we will utilize patient- derived follicular lymphoma samples, two murine models of B-NHL, FDC-deficient mice and antibody blocking experiments to determine the contribution of FDC support to B lymphoma formation, progression and dissemination. Lymphoma cells present in lymphoid and neo-lymphoid microenvironments will be further characterized to identify engaged signaling pathways and gene expression signatures to establish profiles of the lymphoma cells, and provide the framework for future studies to investigate the significance and therapeutic potential of particular signaling nodes and microenvironmental factors.